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''Balamuthia mandrillaris'' is a free-living
amoeba An amoeba (; less commonly spelled ameba or amœba; : amoebas (less commonly, amebas) or amoebae (amebae) ), often called an amoeboid, is a type of Cell (biology), cell or unicellular organism with the ability to alter its shape, primarily by ...
that causes the rare but deadly neurological condition granulomatous amoebic encephalitis (GAE). ''B. mandrillaris'' is a soil-dwelling amoeba and was first discovered in 1986 in the brain of a
mandrill The mandrill (''Mandrillus sphinx'') is a large Old World monkey native to west central Africa. It is one of the most colorful mammals in the world, with red and blue skin on its face and posterior. The species is Sexual dimorphism, sexually ...
that died in the San Diego Wild Animal Park. ''B. mandrillaris'' can infect the body through open wounds or possibly by inhalation. ''Balamuthia'' has been isolated from soil. It is believed to be distributed throughout the soils of temperate regions of the world. This is supported somewhat by the detection of
antibodies An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...
to the
protist A protist ( ) or protoctist is any eukaryotic organism that is not an animal, land plant, or fungus. Protists do not form a natural group, or clade, but are a paraphyletic grouping of all descendants of the last eukaryotic common ancest ...
in healthy individuals. The generic name ''Balamuthia'' was given by Govinda Visvesvara, after his mentor, parasitologist William Balamuth, for his contributions to the study of amoebae. Visvesvara isolated and studied the pathogen for the first time in 1993.


Morphology

''B. mandrillaris'' is a free-living,
heterotroph A heterotroph (; ) is an organism that cannot produce its own food, instead taking nutrition from other sources of organic carbon, mainly plant or animal matter. In the food chain, heterotrophs are primary, secondary and tertiary consumers, but ...
ic amoeba, consisting of a standard complement of
organelle In cell biology, an organelle is a specialized subunit, usually within a cell (biology), cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as Organ (anatomy), organs are to th ...
s surrounded by a three-layered
cell wall A cell wall is a structural layer that surrounds some Cell type, cell types, found immediately outside the cell membrane. It can be tough, flexible, and sometimes rigid. Primarily, it provides the cell with structural support, shape, protection, ...
(thought to be made of
cellulose Cellulose is an organic compound with the chemical formula, formula , a polysaccharide consisting of a linear chain of several hundred to many thousands of glycosidic bond, β(1→4) linked glucose, D-glucose units. Cellulose is an important s ...
or a similar polysaccharide), and with an abnormally large
cell nucleus The cell nucleus (; : nuclei) is a membrane-bound organelle found in eukaryote, eukaryotic cell (biology), cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, have #Anucleated_cells, ...
. On average, a ''Balamuthia'' trophozoite is about 30 to 120 μm in diameter. The cysts fall around this range, as well.


Life cycle

''Balamuthia''s lifecycle, like the ''
Acanthamoeba ''Acanthamoeba'' is a genus of amoeboid, amoebae that are commonly recovered from soil, fresh water, and other habitat (ecology), habitats. The genus ''Acanthamoeba'' has two stages in its life cycle, the metabolically active trophozoite stage a ...
'', consists of a cystic stage and a non-flagellated trophozoite stage, both of which are infectious, and both of which can be identified in the brain tissue on microscopic examination of brain biopsies performed on infected individuals. The trophozoite is pleomorphic and uninucleated, but binucleated forms are occasionally seen. Cysts are also uninucleated, possessing three walls: an outer thin irregular ectocyst, an inner thick endocyst, and a middle amorphous fibrillar mesocyst.


Pathology

''B. mandrillaris'' is larger than human leukocytes, thus making
phagocytosis Phagocytosis () is the process by which a cell (biology), cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs ph ...
impossible. Instead, the immune system attempts to contain them at the portal of entry (usually an open wound) by mounting a
type IV hypersensitivity Type IV hypersensitivity, in the Gell and Coombs classification of allergic reactions, often called delayed-type hypersensitivity, is a type of hypersensitivity reaction that can take a day or more to develop. Unlike the other types, it is not ...
reaction. Upon introduction, the amoeba may form a
skin lesion A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of this ...
, or in some cases, may migrate to the brain, causing a condition known as granulomatous amoebic encephalitis (GAE), which is usually fatal. This granulomatous feature is mostly seen in immunocompetent patients; immunocompromised individuals exhibit a "perivascular cuffing". ''Balamuthia''-induced GAE can cause focal paralysis, seizures, and
brainstem The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is conti ...
symptoms such as facial paralysis, difficulty swallowing, and double vision. ''Balamuthia'' may also cause a variety of non-neurological symptoms, including skin
lesions A lesion is any damage or abnormal change in the tissue of an organism, usually caused by injury or diseases. The term ''Lesion'' is derived from the Latin meaning "injury". Lesions may occur in both plants and animals. Types There is no de ...
, which can progress to GAE. Patients experiencing this particular syndrome may report a skin lesion (often similar to those caused by
MRSA Methicillin-resistant ''Staphylococcus aureus'' (MRSA) is a group of gram-positive bacteria that are genetically distinct from other strains of ''Staphylococcus aureus''. MRSA is responsible for several difficult-to-treat infections in humans. ...
), which does not respond well to
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...
s. The lesion is usually localized and very slow to heal, or fails to heal altogether. In some presentations, this infection may be mistaken for certain forms of
skin cancer Skin cancers are cancers that arise from the Human skin, skin. They are due to the development of abnormal cells (biology), cells that have the ability to invade or metastasis, spread to other parts of the body. It occurs when skin cells grow ...
or
cutaneous leishmaniasis Cutaneous leishmaniasis is the most common form of leishmaniasis affecting humans. It is a skin infection caused by a Trypanosomatid, single-celled parasite that is Vector (epidemiology), transmitted by the bite of a Phlebotominae, phlebotomine s ...
. ''Balamuthia'' lesions are most often painless.


Culturing and identification

Biopsies of skin lesions, sinuses, lungs, and the brain can detect of ''B. mandrillaris'' infection. The
amoeba An amoeba (; less commonly spelled ameba or amœba; : amoebas (less commonly, amebas) or amoebae (amebae) ), often called an amoeboid, is a type of Cell (biology), cell or unicellular organism with the ability to alter its shape, primarily by ...
cannot be cultured on an
agar plate An agar plate is a Petri dish that contains a growth medium solidified with agar, used to Microbiological culture, culture microorganisms. Sometimes selective compounds are added to influence growth, such as antibiotics. Individual microorganism ...
coated with E. coli because, unlike '' Naegleria'' or ''
Acanthamoeba ''Acanthamoeba'' is a genus of amoeboid, amoebae that are commonly recovered from soil, fresh water, and other habitat (ecology), habitats. The genus ''Acanthamoeba'' has two stages in its life cycle, the metabolically active trophozoite stage a ...
'', ''Balamuthia mandrillaris'' does not feed on bacteria. Instead, ''Balamuthia'' must be cultured on primate
hepatocyte A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in: * Protein synthesis * Protein storage * Transformation of carbohydrates * Synthesis of cholesterol, bi ...
s or human brain microvascular
endothelial The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the res ...
cells. Formalin-fixed paraffinized biopsy specimens may indicate ''Balamuthia'' trophozoites in the perivascular space. The cysts can be visualized by calcofluor white, which binds to
polysaccharide Polysaccharides (), or polycarbohydrates, are the most abundant carbohydrates found in food. They are long-chain polymeric carbohydrates composed of monosaccharide units bound together by glycosidic linkages. This carbohydrate can react with wat ...
s on the cyst wall. Trophozoites appear circular during infection.
Vero cell Vero cells are a lineage of cells used in cell cultures. The 'Vero' lineage was isolated from kidney epithelial cells extracted from an African green monkey ('' Chlorocebus'' sp.; formerly called ''Cercopithecus aethiops'', this group of monk ...
s have been suggested as a possible cheaper and faster alternative to culture the organism. Several types of animal cells have been used in ''B. mandrillaris'' culturing including rat glioma cells, human lung cells, and human brain microvascular endothelial cells. These animal cells are added to a specified sterilized growth medium for co culturing with the pathogen. This can also help differentiate between ''Balamuthia'' and other protozoa. Axenic culture methods that are of importance to antiprotozoal
drug development Drug development is the process of bringing a new pharmaceutical drug to the market once a lead compound has been identified through the process of drug discovery. It includes preclinical research on microorganisms and animals, filing for regu ...
have also been reported within the last decade


Treatment

Infection seems to be survivable if treated early. Two individuals, a 5-year-old girl and a 64-year-old man, developed GAE. After diagnosis, they were treated with flucytosine, pentamidine,
fluconazole Fluconazole is an antifungal medication used for a number of fungal infections. These include candidiasis, blastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and tinea versicolor. It is also used to pr ...
,
sulfadiazine Sulfadiazine is an antibiotic. Used together with pyrimethamine, a dihydrofolate reductase inhibitor, it is the treatment of choice for toxoplasmosis, which is caused by a protozoan parasite. It is a second-line treatment for otitis media, pr ...
, a
macrolide Macrolides are a class of mostly natural products with a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. Macrolides belong to the polyketide class of natural products. ...
antibiotic and trifluoperazine. Both patients recovered. In 2018, an unsuccessful attempt at treatment of a ''Balamuthia'' infection after nasal lavage with untreated tap water was reported. Nitroxoline has shown interesting properties ''in vitro'' and might be a possible treatment for this infection. A man treated with nitroxoline at
UCSF Medical Center The UCSF Medical Center is a research and teaching hospital in San Francisco, California, and is a medical center of the University of California, San Francisco. It is affiliated with the UCSF School of Medicine and the UCSF Helen Diller Famil ...
in 2021, following a seizure that was identified to have resulted from CNS invasive Balamuthia infection, survived and recovered from the disease, indicating that nitroxoline might be a promising medication. An opinion article published in the ''
Washington Post ''The Washington Post'', locally known as ''The'' ''Post'' and, informally, ''WaPo'' or ''WP'', is an American daily newspaper published in Washington, D.C., the national capital. It is the most widely circulated newspaper in the Washington m ...
'' in 2025 mentions a pediatric patient who survived and recovered from Balamuthia after being administered nitroxoline.


Organ transplantation

According to a report published in ''
Morbidity and Mortality Weekly Report The ''Morbidity and Mortality Weekly Report'' (''MMWR'') is a weekly epidemiological digest for the United States published by the Centers for Disease Control and Prevention (CDC). It was originally established as ''Weekly Health Index'' in 1930 ...
'' in September 2010, two confirmed cases of ''Balamuthia'' transmission occurred through organ transplantation in December 2009 in
Mississippi Mississippi ( ) is a U.S. state, state in the Southeastern United States, Southeastern and Deep South regions of the United States. It borders Tennessee to the north, Alabama to the east, the Gulf of Mexico to the south, Louisiana to the s ...
. Two kidney recipients, a 31-year-old woman and a 27-year-old man, suffered from post-transplant encephalitis due to ''Balamuthia''. The woman died in February 2010 and the man survived with partial paralysis of his right arm. The CDC was notified by a physician on December 14, 2009, about possible transplant transmission in these two patients. Histopathologic testing of donor and recipient tissues confirmed the transmission. Two other patients who received heart and liver transplants from the same donor, but in different hospitals, were placed on preemptive therapy and remain unaffected. A second cluster of transplant-transmitted ''Balamuthia'' in Arizona was reported in the same weekly report. Four recipients were identified, two from Arizona (liver and kidney-pancreas), one from California (kidney), and another from Utah (heart). Recipients from Arizona—a 56-year-old male and a 24-year-old male—both succumbed to GAE within a span of 40 days from transplantation. The other two were placed on preemptive therapy after the first two were reported and remain unaffected.


References


External links


Balamuthia , Parasites , CDC
for images: Cyst of ''B. mandrillaris'' and Trophozoite of ''B. mandrillaris'' in culture. Credit: DPDx
How one girl was cured of Balamuthia infection
in ''
The Washington Post ''The Washington Post'', locally known as ''The'' ''Post'' and, informally, ''WaPo'' or ''WP'', is an American daily newspaper published in Washington, D.C., the national capital. It is the most widely circulated newspaper in the Washington m ...
'' {{Taxonbar, from=Q1159908 Discosea Parasitic amoebozoa Monotypic eukaryote genera Rare infectious diseases Neglected American diseases Amoebozoa species Protists described in 1993